Patients with essential hypertension have abnormal endothelium-dependent vasodilation due to reduced release of nitric oxide(NO). But it is uncertain whether this defect is selective for some pathways of nitric oxide production or a more generalized abnormality of endothelial function. The purpose of this study was to determine whether this defect is due to an impairment at the specific intracellular signal-transduction pathway level or is a more generalized endothelial dysfunction.

Forearm blood flow was measured in 10 patients with essential hypertension (mean blood pressure, 129±16.6mmHg ; aged 48±10 years old) and 10 control subjects(mean blood pressure, 99.7±6.6mmHg ; aged 41±10 years old) using strain-gauge plethysmography. The endothelium-dependent vasodilators were acetylcholine(7.5, 15, and 30ug/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin(100, 200, and 400ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside(0.8, 1.6, and 3.2ug/min) was used as an endothelium-independent vasodilator. All drugs were infused into the brachial artery and the order was determined randomly.

The maximum flow in response to acetylcholine was markedly impaired in hypertensive patients compared with control subjects(5.29±1.86 vs 11.04±2.46ml/min/100ml forearm tissue, p<0.001). But the maximum forearm blood flow in response to bradykinin was similar in the two groups(11.96±3.57 vs 12.48±1.92ml/min/100ml forearm tissue, p=0.69) and that in response to sodium nitroprusside was also similar(10.63±3.74 vs 10.51±2.39ml/min/100ml forearm tissue, p=0.94).

Patients with essential hypertension have impaired endothelium-dependent vasodilator response only to acetylcholine, while the response to bradykinin is preserved. This finding indicates that the impairment of endothelial vasodilator function is selective, and suggests the defect occurs at the level of the intracellular signal transduction pathway.